Mental health and quality of life in patients with chronic liver disease: a single-center structural equation model.

BACKGROUND: Chronic liver disease (CLD) is one of the leading disease burdens in Pakistan. Until now, there has only been limited focus in the country on providing health services through tertiary services in urban cities, whereas there is almost no research in Pakistan on the mental health and quality of life of CLD patients. This study aimed to understand which predictors influence the mental health and quality of life of CLD patients in order to advise better policy protection. METHODS: Data was collected from CLD patients at the Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan. A total of 850 respondents were part of the final sample. The age of respondents ranged from 18 to 79 years and included the following diagnosis: (i) Chronic Viral Hepatitis (n = 271), (ii) Cirrhosis (n = 259), (iii) Hepatocellular Carcinoma (n = 193), and (iv) Non-viral Liver Disease (n = 127). RESULTS: Mean results reveal that females as well as illiterate patients need more support for mental health and communication with their physician; whereas men need more support to develop coping strategies. Structural equation modelling results reveal that the severity of symptoms (ß = 0.24, p < 0.001), coping strategies (ß=-0.51, p < 0.001), and doctor communication (ß=-0.35, p < 0.001) predict mental health. Quality of life is associated with the severity of symptoms (ß=-0.36, p < 0.001), coping strategies (ß = 0.26, p < 0.05), and doctor communication (ß = 0.09, p < 0.05). CONCLUSIONS: A 'bio-psycho-social-spiritual' model is recommended for Pakistan's CLD patients which includes the integration of social officers to provide support in four key areas to secure mental health and quality of life of patients.

Associations of tumor-related psychiatric symptoms and healthy behaviors with dynamic quality of life after hepatocellular carcinoma hepatectomy.

OBJECTIVE: To assess the independent and combined associations of tumor-related psychiatric symptoms (TRPS) with dynamic health-related quality of life (HRQL) in patients with hepatocellular carcinoma (HCC) after hepatectomy and to identify related patterns of health behaviors. METHODS: This prospective study included patients with HCC who underwent hepatectomy between September 2021 and May 2022. Independent and combined associations between TRPS and HRQL were identified by generalized linear model and weighted quantile sum model, respectively. Trajectories of HRQL were identified by latent class mixed model. RESULTS: Among the 205 patients, 174 (84.9%) were male. For the outcome of HRQL at 6 months: Anxiety, depression, fatigue, and sleep disorder were independently associated with a decrease of HRQL (all P < 0.05). A negative combined effect of TRPS was also found (ß = - 5.07, 95% CI, - 10.01 to - 0.13), with depression emerged as the predominant contributor (49%). The health behaviors of body mass index, smoking, drinking, or physical exercise were not significantly modified the associations between combined TRPS and HRQL (all P > 0.05 for interaction). Similar results were also found for the HRQL at baseline and at 1 and 3 months. Three HRQL trajectory groups were identified: recover (44.9%), poor (44.4%), and deteriorating (10.7%). Deteriorating group was associated with higher incidence of TRPS (all P < 0.05). CONCLUSIONS: TRPS were associated with a decrease of HRQL regardless of healthy behaviors in HCC patients. Therefore, healthy behaviors promotion alone might not substantially increase HRQL associated with TRPS, and other measures tackling TRPS are warranted.

Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial.

BACKGROUND: Single-agent nivolumab showed durable responses, manageable safety, and promising survival in patients with advanced hepatocellular carcinoma in the phase 1-2 CheckMate 040 study. We aimed to investigate nivolumab monotherapy compared with sorafenib monotherapy in the first-line setting for patients with advanced hepatocellular carcinoma. METHODS: In this randomised, open-label, phase 3 trial done at medical centres across 22 countries and territories in Asia, Australasia, Europe, and North America, patients at least 18 years old with histologically confirmed advanced hepatocellular carcinoma not eligible for, or whose disease had progressed after, surgery or locoregional treatment; with no previous systemic therapy for hepatocellular carcinoma, with Child-Pugh class A and Eastern Cooperative Oncology Group performance status score of 0 or 1, and regardless of viral hepatitis status were randomly assigned (1:1) via an interactive voice response system to receive nivolumab (240 mg intravenously every 2 weeks) or sorafenib (400 mg orally twice daily) until disease progression or unacceptable toxicity. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, NCT02576509. FINDINGS: Between Jan 11, 2016, and May 24, 2017, 743 patients were randomly assigned to treatment (nivolumab, n=371; sorafenib, n=372). At the primary analysis, the median follow-up for overall survival was 15·2 months (IQR 5·7-28·0) for the nivolumab group and 13·4 months (5·7-25·9) in the sorafenib group. Median overall survival was 16·4 months (95% CI 13·9-18·4) with nivolumab and 14·7 months (11·9-17·2) with sorafenib (hazard ratio 0·85 [95% CI 0·72-1·02]; p=0·075; minimum follow-up 22·8 months); the protocol-defined significance level of p=0·0419 was not reached. The most common grade 3 or worse treatment-related adverse events were palmar-plantar erythrodysaesthesia (1 [<1%] of 367 patients in the nivolumab group vs 52 [14%] of patients in the sorafenib group), aspartate aminotransferase increase (22 [6%] vs 13 [4%]), and hypertension (0 vs 26 [7%]). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. Four deaths in the nivolumab group and one death in the sorafenib group were assessed as treatment related. INTERPRETATION: First-line nivolumab treatment did not significantly improve overall survival compared with sorafenib, but clinical activity and a favourable safety profile were observed in patients with advanced hepatocellular carcinoma. Thus, nivolumab might be considered a therapeutic option for patients in whom tyrosine kinase inhibitors and antiangiogenic drugs are contraindicated or have substantial risks. FUNDING: Bristol Myers Squibb in collaboration with Ono Pharmaceutical.

A randomized clinical trial of guided self-help intervention based on mindfulness for patients with hepatocellular carcinoma: effects and mechanisms.

BACKGROUND: Compared with face-to-face mindfulness-based interventions (MBIs), online mindfulness interventions may be more convenient for patients with limited resources and can provide self-help mindfulness methods to improve the quality of life of cancer patients. This study investigated the effects of guided self-help mindfulness-based interventions (GSH-MBIs) on psychological distress, quality of life and sleep quality in patients with hepatocellular carcinoma and explored the underlying mechanisms. METHODS: A total of 122 patients with hepatocellular carcinoma were randomly divided into the intervention group or the conventional treatment group. Psychological distress, quality of life, sleep quality, psychological flexibility and perceived stress were evaluated in the groups before the intervention at baseline, after the intervention, at 1-month follow-up and 3-month follow-up. The intervention's effects over time and the potential mediating effects were analysed using generalized estimating equations (GEE). RESULTS: GEE results indicated significant time-group interaction effects on psychological distress (P < 0.001) and sleep quality (P < 0.001). The intervention significantly improved psychological flexibility (ß, -2.066; 95% CI, -3.631, -0.500) and reduced perceived stress (ß, -2.639; 95% CI, -4.110, -1.169). Psychological flexibility and perceived stress played a mediating role in the observed results. CONCLUSION: GSH-MBIs can improve psychological distress and sleep quality via changing the psychological flexibility and perceived stress in hepatocellular carcinoma patients.

Health-related quality-of-life impact of pembrolizumab versus best supportive care in previously systemically treated patients with advanced hepatocellular carcinoma: KEYNOTE-240.

BACKGROUND: Health-related quality of life (HRQoL) is an important outcome measure and prognostic indicator in hepatocellular carcinoma (HCC). KEYNOTE-240 (NCT02702401) assessed the efficacy and safety of pembrolizumab plus best supportive care (BSC) versus placebo plus BSC in patients with HCC who previously received sorafenib. This study presents the results of a prespecified exploratory analysis of patient-reported outcomes. METHODS: Patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and its HCC supplement (EORTC QLQ-HCC18) electronically at baseline; at weeks 2, 3, 4, 6, 9, 12, and 18; and then every 9 weeks until 1 year or end of treatment, and at the 30-day safety follow-up visit. RESULTS: The HRQoL population included 271 and 127 patients randomly assigned to pembrolizumab and placebo, respectively. From baseline to week 12, changes in both scores were similar between pembrolizumab and placebo; global health status/QoL scores were stable. The proportions of patients who improved, remained stable, or deteriorated across all functional domain and symptom scores were generally similar between pembrolizumab and placebo. Time to deterioration was similar between the 2 arms based on the prespecified analysis of EORTC QLQ-HCC18 domains of abdominal swelling, fatigue, and pain. CONCLUSION: Pembrolizumab preserved HRQoL during treatment for advanced HCC. Combined with efficacy and safety results from KEYNOTE-240, these findings support a positive benefit/risk profile for pembrolizumab in a second-line treatment setting for patients with HCC who previously received sorafenib.

A closer look at quality of life in the hepatocellular carcinoma literature.

PURPOSE: Adults with hepatocellular carcinoma (HCC) have a high symptom burden. Their quality of life (QOL) has been shown to be significantly impacted by both the disease and its treatment, adding to the high symptom burden that these patients experience. The primary aims of this paper are as follows: (1) to identify how QOL is being defined in HCC literature and (2) to identify how QOL is being measured in the HCC literature using Ferrell's model of QOL. METHODS: A systematic review was completed of relevant studies published after 2014, using PubMed, CINHAL, and PsycInfo. Relevant studies were reviewed by 2 reviewers using PRISMA guidelines. RESULTS: From a total of 1312 papers obtained in the initial database search, 30 met inclusion criteria and are included in this review. From the included articles, 10% included a definition of QOL and 3% addressed the spiritual domain of QOL. Majority of study participants were in the early stage of HCC, though the majority of adults with HCC are diagnosed in the advanced stage. Only 3% of included studies included greater than 22% population of advanced stage of HCC. CONCLUSION: The results of this systematic review demonstrate the need for future research into QOL in the advanced stage of QOL. It also identified gap in the literature concerning the definition of QOL in HCC and the spiritual domain of QOL in HCC.

A mixed-methods approach to understanding perceptions of hepatitis B and hepatocellular carcinoma among ethnically diverse Black communities in South Florida.

PURPOSE: Hepatitis B (HBV), the leading cause of hepatocellular carcinoma (HCC), disproportionately affects minorities. Compared to other races, Blacks more often present with advanced HCC and have decreased survival. We observed higher HBV-associated HCC rates among Blacks than reported nationally. In our center, Haitian Blacks had the highest rates of HBV-associated HCC and shorter survival compared to other Blacks. We investigated knowledge and perceptions regarding HBV and HCC among Blacks born in the United States or Haiti. METHODS: Using community partnerships, participants were recruited via word of mouth, email, social media or from Hepatology clinic. Focus groups were conducted in Haitian Creole or English and stratified by birthplace, gender and infection status. Discussions were audio-recorded and transcribed verbatim. A constant comparative method was used for data analysis; themes are based on conversational details. RESULTS: There were 55 participants; 49% were male and 27% had chronic HBV. Only 42% of Haitian Blacks knew about HBV prior to participation vs. 78% of African Americans, p 0.03. Both groups expressed that fear, mistrust of the medical establishment, denial and stigma might compel persons to avoid seeking care. Both groups attributed higher rates of late stage HCC diagnosis in Blacks to inadequate financial resources and education. Those with HBV reported confusion regarding their infection and suboptimal communication with healthcare providers. CONCLUSIONS: In two communities disproportionately affected by HBV, misconceptions about disease transmission, stigma, low health literacy and decreased access to care may limit detection for HBV. Culturally relevant community-based interventions are needed to increase HBV detection.

Outcomes in hepatocellular carcinoma patients undergoing sorafenib treatment: toxicities, cellular oxidative stress, treatment adherence, and quality of life.

The study of toxicities induced by sorafenib, as well as the identification of possible mechanisms and biomarkers of these toxicities, is important to improve the treatment and quality of life of hepatocellular carcinoma (HCC) patients. This study focused on toxicities, cellular oxidative stress, adherence, and quality of life of 11 patients with HCC treated with sorafenib. Dermatotoxicity, myelotoxicity, gastro toxicity, nephrotoxicity, pain, and fatigue were investigated. For oxidative stress analysis, the peripheral blood mononuclear cells were isolated and mitochondrial superoxide anion production was measured using MitoSOX Red test. Medication adherence was evaluated based on Morisky-Green and MedTake tests. Quality of life assessment was performed using EORTC QLQ C-30 and QLQ HCC18 questionnaires. The results showed that hand-foot syndrome (45.5%), thrombocytopenia (45.5%), diarrhea (54.5%), pain (54.5%), and fatigue (36.4%) were the most prevalent toxicities. A non-statistically significant change in the levels of superoxide anion was observed after the sorafenib treatment (Wilcoxon test, P = 0.4131). Moreover, 81.8% of patients had high adherence, 100% knew the correct indication of sorafenib, 81.8% knew the correct intake and drug regimen, and 36.4% knew the correct dose of antineoplastic. There was a significant worsening in the emotional and pain domains of quality of life after the sorafenib (Wilcoxon test, P = 0.0313 and P = 0.0313, respectively). A production of superoxide anion was not correlated with toxicities (Spearman's correlation and Mann-Whitney U tests, P > 0.05). This study suggests that oxidative stress might not be the mechanism of sorafenib toxicities.

High incidence of hepatocellular carcinoma and cirrhotic complications in patients with psychiatric illness: a territory-wide cohort study.

BACKGROUND: Because of high-risk behaviours, sedentary lifestyle and side effects of medications, psychiatric patients are at risk of viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease. We aimed to study the incidence of hepatocellular carcinoma (HCC) and cirrhotic complications in psychiatric patients. METHODS: We identified consecutive adult patients in all public hospitals and clinics in Hong Kong with psychiatric diagnoses between year 2003 and 2007 using the Clinical Data Analysis and Reporting System, which represents in-patient and out-patient data of approximately 80% of the 7.4-million local population. The patients were followed for liver-related events (HCC and cirrhotic complications) and deaths until December 2017. Age- and sex-standardized incidence ratio (SIR) of HCC in psychiatric patients to the general population was estimated by Poisson model. RESULTS: We included 105,763 psychiatric patients without prior liver-related events in the final analysis. During a median (interquartile range) follow-up of 12.4 (11.0-13.7) years, 1461 (1.4%) patients developed liver-related events; 472 (0.4%) patients developed HCC. Compared with the general population, psychiatric patients had increased incidence of HCC (SIR 1.42, 95% confidence interval [CI] 1.28-1.57, P < 0.001). The SIR was highest in patients with drug-induced (SIR 3.18, 95% CI 2.41-4.11, P < 0.001) and alcohol-induced mental disorders (SIR 2.98, 95% CI 2.30-3.81, P < 0.001), but was also increased in patients with psychotic disorders (SIR 1.39, 95% CI 1.16-1.65, P < 0.001) and mood disorders (SIR 1.16, 95% CI 1.00-1.34, P = 0.047). Liver disease was the fifth most common cause of death in this population, accounting for 595 of 10,614 (5.6%) deaths. Importantly, 569 (38.9%) patients were not known to have liver diseases at the time of liver-related events. The median age at HCC diagnosis (61 [range 26-83] years) was older and the median overall survival (8.0 [95% CI 5.0-10.9] months) after HCC diagnosis was shorter in this cohort of psychiatric patients than other reports from Hong Kong. CONCLUSIONS: HCC, cirrhotic complications, and liver-related deaths are common in psychiatric patients, but liver diseases are often undiagnosed. More efforts are needed to identify liver diseases in the psychiatric population so that treatments and screening for HCC and varices can be provided to patients in need.

Impact of the disclosure of diagnosis on posttraumatic stress and growth and quality of life in Chinese patients with hepatocellular carcinoma.

PURPOSE: To evaluate the impact of disclosure/nondisclosure of cancer diagnosis on patients' posttraumatic stress symptoms (PTSS), posttraumatic growth (PTG), and quality of life (QOL). METHODS: Patients with primary hepatocellular carcinoma (HCC) who were admitted for potentially curative treatments in a teaching hospital were recruited. Patients were interviewed at admission regarding their QOL and their attitude towards disclosure of diagnosis. They were interviewed again for QOL, PTSS, and PTG at discharge and at 1 month after discharge. RESULTS: There were 300 patients recruited, 88.3% of whom preferred disclosure of cancer diagnosis. In fact, 162 patients (54.0%) received disclosure of their cancer diagnosis before discharge (disclosed group). However, for the 138 patients whose diagnoses were concealed by their families (uninformed group), 116 patients (84.1%) had learned of their diagnosis of HCC independently within 1 month after discharge. Comparing the scores at 1 month after discharge with scores at discharge showed that the PTSS score significantly declined for patients in the disclosed group and the PTG score significantly decreased for the uninformed patients at 1 month after discharge (p < 0.001 for both comparisons). Additionally, compared with the uninformed group, patients in the disclosed group had lower scores for PTSS (p < 0.001), higher scores for PTG (p < 0.001), better emotional functioning (p < 0.001), and better global QOL (p = 0.006) at 1 month after discharge. CONCLUSIONS: Our findings indicate that concealing the diagnosis of cancer from patients is unlikely to succeed. Additionally, disclosure of diagnosis is beneficial for HCC patients in reducing PTSS and improving PTG and QOL.

Genetic variation in NRG 1 gene and risk of post-traumatic stress disorders in patients with hepatocellular carcinoma.

OBJECTIVE: Neuregulin 1 (NRG1) was proved to play an important role in numerous neurodevelopmental processes. In our study, we aimed to investigate the relationship between the NRG1 gene polymorphism and the cognitive function of patients with hepatocellular carcinoma (HCC) complicated with post-traumatic stress disorders (PTSD) before and after the psychological intervention. METHODS: Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) were used for cognitive function assessment. Serum level of NRG1 was detected by ELISA, and the correlation between NRG1 level and cognitive function was analyzed. The difference of cognitive function score of patients with HCC complicated with PTSD before and after psychological intervention was compared, and the relationship between rs35753505 and rs3924999 polymorphism with the score was analyzed. RESULTS: Patients with HCC complicated with PTSD showed decreased serum NRG1 level. NRG1 levels of patients in the HCC + PTSD group were positively correlated with MMSE, MoCA, and LOTCA scores. In rs35753505, the CC genotype was a risk factor for the occurrence of PTSD in patients with HCC, while in rs3924999, the GG genotype was a risk factor for the occurrence of PTSD in patients with HCC. After psychological intervention, the CC genotype at rs35753505 and the GG genotype at rs3924999 were susceptible genotypes. CONCLUSION: CC genotype at rs35753505 and GG genotype at rs3924999 of NRG1 gene increased the risk of PTSD in patients with HCC. CC and GG genotypes were susceptible after psychological intervention.

Clinico-Psychosocial Factors Predicting Hepatocellular Carcinoma Related Knowledge Among Patients with Chronic Liver Disease.

Regular clinical surveillance for hepatocellular carcinoma (HCC) among high-risk patients could lead to early detection and cure. Patient's knowledge and attitude are important to the uptake rate of this surveillance. This study is aimed at assessing the level of HCC-related knowledge among patients with chronic liver disease (CLD) who are at risk of HCC and determine predictors for poor knowledge. A cross-sectional study was conducted among inpatients with CLD at the Third People's Hospital of Kunming in China. Questionnaires were used to measure patient's sociodemographic characteristics, HCC-related knowledge, and patient-doctor-related psychometric factors. Factor analysis was performed to explore the underlying domains captured by the knowledge questionnaire. Univariate and multivariate analyses were performed to identify independent predictors for each domain. Three common factors were derived from the exploratory factor analysis, namely, "Surveillance," "Lifestyle," and "Prognosis." Patients with low educational background and a short period of having CLD were at a significantly low level of HCC-related knowledge of all three domains. On the other hand, surveillance and lifestyle but not prognosis, were associated with patient's communication confidence with doctors. Over two-thirds of high-risk patients had low knowledge of HCC. Medical providers should pay more attention to low educational groups and newly diagnosed CLD patients.

Functional rs6265 polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in posttraumatic stress disorder among Chinese patients with hepatocellular carcinoma.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that plagues trauma survivors. Evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the occurrence and development of PTSD. Here we tried to demonstrate whether BDNF gene polymorphisms are correlated with neurocognitive function following PTSD in patients with hepatocellular carcinoma (HCC). This study included 102 patients with HCC complicated with PTSD, 146 HCC patients, and 152 healthy volunteers. Initially, we evaluated the neurocognitive function of the study subjects. Next, we measured BDNF G11757C and rs6265 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The correlation of BDNF polymorphisms and BDNF level with HCC complicated with PTSD was evaluated. The results revealed that HCC complicated with PTSD showed decreased serum BDNF level and Mini-mental state examination (MMSE) score. Serum BDNF level of HCC and HCC complicated with PTSD was positively correlated with MMSE score. GA + AA allele and A allele of rs6265 increased the risk of PTSD among patients with HCC. GA and AA genotypes of rs6265 were correlated with the decreased MMSE score of HCC complicated with PTSD. Haplotype GA of rs6265 and G11757C increased the risk of PTSD for HCC, while haplotype CG decreased this risk. Lastly, the logistic regression analysis suggested that low BDNF level was a contributor to HCC complicated with PTSD, while GG genotype of rs6265 served as a protective factor. Collectively, this study defines the GG genotype of BDNF rs6265 polymorphism as a protector to HCC complicated with PTSD. In addition, these results provided a promising target for PTSD prevention in patients with HCC.

Socioeconomic disparities of depressive symptoms and cytokines in hepatocellular carcinoma.

OBJECTIVE: To examine the associations among socioeconomic factors, depressive symptoms, and cytokines in patients diagnosed with hepatocellular carcinoma (HCC). METHODS: A total of 266 patients diagnosed with HCC were administered a battery of questionnaires including a sociodemographic questionnaire and the Center for Epidemiologic StudiesDepression (CES-D) scale. Blood samples were collected to assess serum levels of cytokines using Luminex. Descriptive statistics, Mann-Whitney U, Kruskal-Wallis, linear regression, and Bonferroni corrections were performed to test the hypotheses. RESULTS: Of the 266 patients, 24% reported depressive symptoms in the clinical range (CES-D ≥ 22). Females had higher CES-D score than males (Mann-Whitney U = 7135, P = .014, Padj  = .028). Being unemployed/disabled (Kruskal-Wallis = 14.732, P = .001, Padj  = .005) was found to be associated with higher depressive symptoms in males but not in females. Serum level of IL-2 (Kruskal-Wallis = 17.261, P = .001, Padj  = .005) were found to be negatively associated with education level. Gender (ß = .177, P = .035), income (ß = -.252, P = .004), whether the patient's income met their basic needs (ß = .180, P = .035), and IL-1ß (ß = -.165, P = .045) independently predicted depressive symptoms and together explained 19.4% of variance associated with depressive symptoms. CONCLUSIONS: Sociodemographic and socioeconomic factors were predictive of inflammation and depressive symptoms. Recommendations include the development of gender-targeted interventions for patients diagnosed with HCC who have low socioeconomic status (SES) and may suffer from depressive symptoms.

The effect of liver transplantation on patient-centred outcomes: a propensity-score matched analysis.

It is unclear whether liver transplantation confers an increase in health-related quality of life (HR-QoL) across all dimensions of health. This study aimed to estimate the effect of liver transplantation on HR-QoL. Pre- and post-transplantation patients attending an outpatient clinic were invited to complete the condition-specific 'Short form of liver disease QOL' questionnaire. Mixed-effect linear regression and propensity-score matching (PSM) on pretransplantation characteristics were used to estimate the difference in overall HR-QoL associated with transplantation. Of 454/609 (74.5%) eligible patients who were included in the analysis, 102 (22.5%) patients fall under pretransplantation category, and 352 (77.5%) were under post-transplantation category. Overall HR-QoL post-transplantation significantly increased in patients without hepatocellular carcinoma (HCC) (ß = 16.84, 95% CI: 13.33 to 20.35, P < 0.001), but not with HCC (ß = 1.25, 95% CI: -5.09 to 7.60, P = 0.704). Donation after circulatory death (DCD) organ recipients had a significantly lower HR-QoL (ß = -4.61, 95% CI: -8.95 to -0.24, P = 0.043). Following PSM, transplantation was associated with a significant increase in overall HR-QoL (average treatment effect: 6.3, 95% CI: 2.1-10.9). There is a significant improvement in HR-QoL attributable to transplantation in this cohort. Post-transplantation HR-QoL was affected by several factors, including HCC status and DCD transplantation, which has important implications for counselling prior to liver transplantation.

Prognostic association of demographic and clinical factors with the change rates of symptoms and depression among patients with hepatocellular carcinoma.

PURPOSE: To identify the predictive value of demographic and clinical factors for determining changes in physical and depressive symptom among hepatocellular carcinoma (HCC) patients over time. METHODS: We performed a prospective cohort study of 128 patients newly diagnosed with HCC in Taiwan. Each patient had four time-point data after the follow-up. Patients' physical symptoms were evaluated with the Edmonton Symptom Assessment System (ESAS). Psychological symptoms were evaluated with the Hospital Anxiety and Depression Scale (HADS). Clinical factors and demographic characteristics were predictors of physical and psychological symptoms, as estimated by a generalized estimating equation (GEE). RESULTS: We found that patients who had a smoking habit and Barcelona Clinic Liver Cancer (BCLC) Stage B disease underwent radiofrequency ablation therapy (RFA) or liver resection, and those who had higher alanine aminotransferase (GPT) level reported more symptoms from baseline to 1 month. Symptoms increased from baseline to 3 months in elderly patients and patients with higher GPT levels. Additionally, patients who had jobs, underwent liver resection, and had BCLC Stage C disease had increased symptoms of depression from baseline to 1 month; in particular, BCLC Stage D disease had negative long-term effects on depression scores from baseline to four-time points following therapy. CONCLUSION: Advanced BCLC stage and undergoing RFA or liver resection were most closely associated with worsening physical and psychological symptoms over time. Clinical professionals should pay attention to these factors that affect physical and psychological symptoms during treatment.

Status of inflammation in relation to health related quality of life in hepatocellular carcinoma patients.

PURPOSE: Both Inflammation and health-related quality of life (HRQoL) are independent prognosticators in HCC patients. We hypothesized that inflammation can cause impairment in HRQoL and investigated the correlation between inflammatory status and HRQoL in HCC patients. METHODS: Clinical, laboratory and HRQoL (using EORTC QLQ-C30, QLQ-HCC18, C30 and HCC18 index-scores) data were prospectively collected from HCC patients at diagnosis. Correlation analyses were performed between HRQoL and inflammation-based markers including C-reactive protein (CRP), CRP/albumin ratio (CRP/alb), Glasgow Prognostic Score (GPS), Inflammation-Based Index (IBI) and Prognostic Index (PI). RESULTS: Among 445 HCC patients, higher inflammatory states were significantly correlated with worse HRQoL. For CRP and CRP/alb ratio, the HRQoL factors with higher correlations included C30 and HCC18 index-scores, certain QLQ-C30 domains and items ('physical functioning', 'role functioning', 'fatigue', 'pain', 'appetite loss') and QLQ-HCC18 items ('fatigue', 'body image', 'nutrition' and 'abdominal swelling'), where the Pearson's correlation coefficients were up to 0.416. Multivariate analyses indicated that worse HRQoL factors were significantly correlated with worse scores in GPS, IBI and PI. CONCLUSION: In HCC patients, inflammatory status correlates with HRQoL at presentation. In particular, relatively stronger correlations with CRP-based markers have been observed in HRQoL scales that assess constitutional symptoms (QLQ-C30 'physical functioning', 'role functioning', 'fatigue', 'appetite loss' and QLQ-HCC18 'fatigue' and 'nutrition') and tumor burden (QLQ-C30 'pain' and QLQ-HCC18 'abdominal swelling' and 'body image'). Future studies are warranted to evaluate whether intervention that reduces inflammation could improve HRQoL in HCC patients.

Prognostic values of EORTC QLQ-C30 and QLQ-HCC18 index-scores in patients with hepatocellular carcinoma - clinical application of health-related quality-of-life data.

BACKGROUND: Health-related quality-of-life (HRQOL) assessment with EORTC QLQ-C30 was prognostic for overall survival (OS) in patients with advance-stage hepatocellular carcinoma (HCC), but no data existed for early-stage patients. The HCC-specific QLQ-HCC18 has not been evaluated for prognostic value in HCC patients. Utilization of raw HRQOL data in clinical setting has been impractical and non-meaningful. Therefore we developed index scores of QLQ-C30 and QLQ-HCC18 in an attempt to enable clinical utilization of these HRQOL measurements. This study investigates the prognostic significance of QLQ-C30, QLQ-HCC18 and C30/HCC18 index-scores in patients with newly diagnosed HCC which encompasses all stages. METHODS: From 2007-2011, 517 patients were prospectively recruited. HRQOL was assessed at diagnosis using QLQ-C30 and QLQ-HCC18; C30 and HCC18 index-scores were calculated from raw HRQOL data. Cox regression was performed using continuous, dichotomized QLQ-C30 and QLQ-HCC18 variables, or index-scores, together with clinical factors to identify independent factors for OS. Various multivariate models were validated with c-index and bootstrapping for 1000 replications. RESULTS: Four hundred and seventy two patients had complete HRQOL data. Their median OS was 8.6 months. In multivariate analysis, independent prognostic HRQOL variables for OS were QLQ-C30 pain (HR 1.346 [1.092-1.661], p = 0.0055), QLQ-C30 physical functioning (HR 0.652 [0.495-0.860], p = 0.0024); QLQ-HCC18 pain (HR 1.382 [1.089-1.754], p = 0.0077) and QLQ-HCC18 fatigue (HR 1.441 [1.132-1.833], p = 0.0030). C30 index-score (HR 2.143 [1.616-2.841], p < 0.0001) and HCC18 index-score (HR 1.957 [1.411-2.715], p < 0.0001) were highly significant factors for OS. The median OS of patients with C30 index-score of 0-20, 21-40, 41-60, 61-100 were 16.4, 7.3, 3.1, 1.8 months respectively (p < 0.0001); while for HCC18 index-score: 16.4, 6.0, 2.8, 1.8 months respectively (p < 0.0001). All the multivariate models were validated, with mean optimism <0.01. The bootstrap validated c-index was 0.78. CONCLUSIONS: QLQ-C30 and QLQ-HCC18 were prognostic for OS in patients with newly diagnosed HCC irrespective of stage. Both C30 and HCC18 index-scores were highly significant prognostic factors for OS in newly diagnosed HCC patients. Index-scoring provides an effective way to summarize, analyze and interpret raw HRQOL data, and renders QLQ-C30 and QLQ-HCC18 meaningful and communicable in clinical practice. Index-scores could potentially serve as a standardized tool for future HRQOL research.

Anxiety and serum catecholamines as predictors of survival and recurrence in hepatocellular carcinoma.

OBJECTIVE: Increasing evidence suggests that psychological factors are involved in tumor progression. This study investigated the influence of anxiety and serum catecholamines (CAs) on the prognosis of hepatocellular carcinoma (HCC). METHOD: We enrolled 110 HCC patients who underwent tumor resection at the Affiliated Hospital of Nantong University, China, in this long-term investigation between 2005 and 2009. We evaluated anxiety using the Hamilton Anxiety Rating Scale (HAMA) and analyzed CA levels using an ELISA kit. We then assessed the association of each of them with overall survival (OS) and time to recurrence (TTR), as well as with other clinical variables. RESULTS: The HAMA scores significantly correlated with metastasis (P = 0.015), hepatitis B surface antigens (HBsAg) (P = 0.045), and the tumor-node-metastasis stage (P = 0.032), whereas the CA levels also significantly associated with tumor differentiation (P < 0.001). Univariate and multivariate analyses revealed that HAMA scores and CA levels were significant predictors of OS and TTR in HCC patients, with high levels of each being strongly correlated with poor prognosis. CONCLUSION: The HAMA scores and the CA levels were elevated in HCC patients and correlated with OS and TTR, suggesting that they are candidate prognostic markers of HCC.

Estimation of utility weights for major liver diseases according to disease severity in Korea.

BACKGROUND: The global burden of liver diseases, such as hepatocellular carcinoma and liver cirrhosis, is substantial. In this study, we estimated utility weights of liver disease-related health states in the general population using a visual analogue scale (VAS) and the standard gamble (SG) method. METHODS: Depictions of standardized health states related to major liver diseases were developed based on patient education materials and previous publications. To fully reflect disease progression from diagnosis to prognosis, each health state comprised four parts: diagnosis, symptoms, treatment, and progression and prognosis. A total of 407 participants from the Korean general population evaluated the health states using the VAS and SG methods in computer-assisted personal interviews. After excluding illogical responses, mean utility weights were calculated for each health state. RESULTS: The utility weights for health states were significantly different according to the existence of inconsistency in general. According to the VAS results, the health state with the highest utility was 'Chronic hepatitis B virus infection' (0.64), whereas the health state with the lowest utility was 'Hepatocellular carcinoma that requires palliative therapy' (0.17). Similarly, the SG results revealed that the health state with the highest utility was 'Chronic hepatitis B virus infection' (0.85), and the health state with the lowest utility was 'Hepatocellular carcinoma that requires palliative therapy' (0.40). CONCLUSIONS: The estimated utility weights in this study will be useful to measure the burden of liver diseases and evaluate cost-utility of programs for reducing the burden of liver diseases.